a study to evaluate atp150/atp152, vsv-gp154 and ezabenlimab in patients with kras g12d/g12v mutated pdac (kisima-02)

Conditions: Pancreatic Ductal Adenocarcinoma

Summary: the goal of this clinical trial is to test an experimental treatment (immunotherapy) in pancreatic cancer patients. the main research objectives are: * to evaluate if the kisima-02 treatment is safe and well-tolerated (first part) * to evaluate if the kisima-02 treatment has an impact on the time to observe a possible reappearance of the tumor (second part) participants will receive: i) a therapeutic protein vaccine atp150 or atp 152 ii) a viral vector vsv-gp154 iii) an immune checkpoint inhibitor ezabenlimab in the second part of the study, researchers will compare treatment group versus observational group.

this is an open-label, phase 1b study to evaluate the safety, tolerability, immunogenicity and preliminary efficacy of a heterologous prime-boost vaccine (protein and viral vector) regimen without/with the pd-1 inhibitor ezabenlimab. completed - part a (metastatic and locally advanced pdac patients) cohort a: atp150/atp152 and vsv-gp154 treatment ongoing - part b (locally advanced and resected pdac patients) cohort b: atp150/atp152, ezabenlimab and vsv-gp154 treatment cohort b1, b2, b3: dose escalation not started yet - part c (resected pdac patients) cohort c: atp150/atp152, ezabenlimab and vsv-gp154 treatment (treatment versus observational arm)

Eligibility criteria:
key inclusion criteria * histologically or cytologically confirmed pancreatic ductal adenocarcinoma (pdac) with kras g12d or kras g12v mutation. * ecog performance status of 0 or 1. * patients with advanced or metastatic disease who completed at least 16 weeks of standard systemic chem-/chemoradiotherapy and achieved a partial response or stable disease. * patients who underwent confirmed r0 or r1 resection and completed at least 3 months of combined peri-adjuvant multiagent chemotherapy. * no evidence of disease progression or recurrence. * start of study treatment within 12 weeks from the last curative treatment (resected pdac). * life expectancy at least 12 months (resected pdac), or at least 6 months (advanced/metastatic pdac). * archival tumor tissue availability for central kras analysis. key exclusion criteria * not yet recovered from surgery (resected pdac). * gastro-intestinal bowel obstruction. * other malignancy within the last 3 years. * prior chemotherapy or targeted small molecule therapy within 14 (locally advanced/metastatic pdac) or 28 (resected pdac) days from initiation of study treatment. * prior radiotherapy within 14 (advanced/metastatic pdac) or 28 (resected pdac) days from initiation of study treatment. * prior use of immunotherapeutic agents, including but not limited to checkpoint inhibitors or vsv-based agents. * diagnosis of immunodeficiency. * chronic systemic treatment with steroids or other immunosuppressive medications. * active autoimmune disease requiring systemic treatment within the last 2 years. * use of tamoxifen within 1 month prior to start of study treatment

Keywords: kisima-02 pdac atp150 atp152 ezabenlimab vsv-gp154 adjuvant setting resected pancreatic ductal adenocarcinoma metastatic pancreatic ductal adenocarcinoma locally advanced pancreatic ductal adenocarcinoma resected pdac metastatic pdac lapc